This invention relates to 6-amido-3-substituted-1-azabicyclo[3.2.0]hept-2-en-7-one-2-carboxylic acids and their pharmaceutically acceptable salt, ester and amide derivatives (I) which are useful as antibiotics: ##STR2## wherein R.sup.1 is hydrogen or an acyl radical known to be effective in the related bicyclic .beta.-lactam antibiotic art such as the penicillins and cephalosporins, X is halo such as chloro or bromo, oxygen (the 2-3 bond is saturated and the species I exists as a carboxylate salt or ester), or --OR wherein R is, inter alia, acyl, alkyl, or aralkyl. The radicals R.sup.1 and X are more fully defined below. It will be recognized that when X is oxygen, the species I exhibits enol-keto tautomerism wherein the substituent X may also assume the value of --OH.
This invention also relates to carboxylate derivatives of I which are also antibiotics and which may be represented by the following generic structure: ##STR3## wherein X' is oxygen, sulphur or NR' (R'=H or loweralkyl having 1-6 carbon atoms); and R.sup.7 is, inter alia, representatively selected from the group consisting of hydrogen, conventional blocking groups such as trialkylsilyl, acyl and the pharmaceutically acceptable salt, ester and amide moieties known in the bicyclic .beta.-lactam antibiotic art; the definition of R.sup.7 is given in greater detail below.
This invention also relates to processes for the preparation of such compounds (I); pharmaceutical compositions comprising such compounds; and to methods of treatment comprising administering such compounds and compositions when an antibiotic effect is indicated.
There is a continuing need for new antibiotics. For unfortunately, there is no static effectiveness of any given antibiotic because continued wide scale usage selectively gives rise to resistant strains of pathogens. In addition, the known antibiotics suffer from the disadvantage of being effective only against certain types of microorganisms. Accordingly the search for new antibiotics continues.
Thus, it is an object of the present invention to provide a novel class of antibiotics which are useful in animal and human therapy and in inaminate systems. These antibiotics are active against a broad range of pathogens which representatively include both gram positive bacteria such as S. aureus, Strep. pyogenes and B. subtilis, and gram negative bacteria such as E. coli, Proteus morganii, Pseudomonas, Serratia and Klebsiella. Further objects of this invention are to provide chemical processes for the preparation of such antibiotics and their non-toxic pharmaceutically acceptable salts; pharmaceutical compositions comprising such antibiotics and to provide methods of treatment comprising such antibiotics and compositions when an antibiotic effect is indicated.